Induction of antitumor effect on human esophageal carcinoma cells by the retroviral expression of granulocyte macrophage-colony stimulating factor gene.
We have examined antitumor effect of human esophageal carcinoma cells (T.Tn) which were retrovirally transduced to express mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) gene. Nude mice inoculated with T.Tn cells secreting mGM-CSF developed small tumors but the tumors regressed spontaneously, although the proliferation in vitro of transduced cells was not different from that of wild-type cells. In contrast, the tumor of T.Tn cells transduced with human GM-CSF grew as that of wild-type cells, since murine GM-CSF receptors do not bind to human GM-CSF. Histological examination of the regressing tumor of mGM-CSF-producing T.Tn cells revealed predominant infiltration of inflammatory cells including macrophages. In addition, local injection of mGM-CSF-producing T.Tn cells into the established wild-type tumors significantly induced the retardation of subsequent wild-type tumor growth, suggesting that T-cell independent local response plays a crucial role in destroying tumor cells.
Sugaya
M
M
Department of Surgery (II), School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan.
Tagawa
M
M
Matsubara
H
H
Gunji
Y
Y
Takenaga
K
K
Maeda
T
T
Koide
Y
Y
Asano
T
T
Ochiai
T
T
Isono
K
K
Sakiyama
S
S
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000628:therapy; D016207:Cytokines / Q000502:physiology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000628:therapy; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D011788:Quality of Life; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology; D014161:Transduction, Genetic
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor